{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:08:29Z","timestamp":1790510909832,"version":"4.1.0"},"posted":{"date-parts":[[2026,4,22]]},"group-title":"Bioengineering","reference-count":108,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"U.S. National Science Foundation","doi-asserted-by":"crossref","award":["2432379"],"award-info":[{"award-number":["2432379"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000001","name":"U.S. National Science Foundation","doi-asserted-by":"crossref","award":["2404334"],"award-info":[{"award-number":["2404334"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000001","name":"U.S. National Science Foundation","doi-asserted-by":"crossref","award":["2235455"],"award-info":[{"award-number":["2235455"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]},{"award":["DA060543"],"award-info":[{"award-number":["DA060543"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["GM141931"],"award-info":[{"award-number":["GM141931"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01GM106137"],"award-info":[{"award-number":["R01GM106137"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F-2120"],"award-info":[{"award-number":["F-2120"]}],"id":[{"id":"https:\/\/ror.org\/00np6vq88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"crossref","award":["RP210088"],"award-info":[{"award-number":["RP210088"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Rapid pathogen evolution threatens public health by eroding the effectiveness of vaccines, therapeutics, and diagnostic tools. Although spike protein targeting monoclonal antibodies (mAbs) were developed within 10-12 months of the initial outbreak to serve as key theranostic agents, their redesign has struggled to keep pace with viral evolution, rendering many neutralizing antibodies ineffective. Here we demonstrate a novel platform that combines a random-rational hybrid library diversification with high-throughput\n                  <jats:italic>MiSeq<\/jats:italic>\n                  screening to rapidly reprogram aptamers against emerging SARS-CoV-2 spike variants. Interactions between 3 different spike proteins and 11,806 unique aptamer variant designs were profiled within a few days. Starting from a 40-nt aptamer originally selected against wild-type (WT) spike protein, our screen identified a Delta-binding mutant with a 4-fold affinity improvement and an Omicron-binding mutant that converted undetectable binding into nanomolar affinity. We also identified a WT-selective mutant with substantially reduced affinity for Delta, as well as previously unrecognized bases that critically contribute to spike recognition. Integrating high-throughput binding data with molecular dynamics simulations further revealed sequence-dependent structural features underlying variant-specific aptamer-spike interactions. Finally, we developed a sensor based on the identified WT-selective aptamer mutant, enabling highly specific detection of the WT spike protein with robust performance. Together, this work establishes a rapid and adaptable aptamer engineering platform for rapid adaptation of aptamers to evolving pathogens in future pandemics.\n                <\/jats:p>","DOI":"10.64898\/2026.04.21.719937","type":"posted-content","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T03:40:13Z","timestamp":1776915613000},"source":"Crossref","is-referenced-by-count":2,"title":["A High-Throughput Platform for Rapid Adaptation of DNA Aptamers to SARS-CoV-2 Evolution"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6984-3052","authenticated-orcid":false,"given":"Yujie","family":"He","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenglin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-An","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Fonseca-Albert","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle K.","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Ru","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Seifi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7618-9052","authenticated-orcid":false,"given":"Soonwoo","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 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